Pulmonary arterial hypertension (PAH) is a progressive disease, eventually leading to right heart failure and death, with symptoms and mortality comparable to heart failure. There are two main types of PAH; primary PAH and secondary PAH. Primary PAH is of unknown etiology and is thought to be genetic in nature. Secondary PAH arises from known causes and can be associated with exposure to toxins, use of appetite suppressants or effects from diseases such as congenital heart disease, HIV, scleroderma, sickle cell disease and chronic liver disease. The estimated prevalence of PAH in 2007 in Europe, the U.S., and Japan is about 146,000.
In general, PAH results from narrowing or constriction of the pulmonary artery lumen, which results in increased pulmonary vascular resistance and increased pulmonary arterial pressures. This can also lead to increased afterload to the right ventricle, decreased cardiac output, increased right ventricle pressure and increased right ventricle size, ultimately leading to right ventricular failure. In patients with PAH, pressure in the right ventricle and pulmonary artery can be markedly increased relative to healthy individuals without PAH. For example, systolic pressure in the right ventricle may be about 75 mm Hg, while diastolic pressure tends to be only slightly elevated. Systolic pressure in the pulmonary artery may also be in about 75 mm Hg. Diastolic pulmonary arterial pressure may be around 30 mm Hg.
A number of therapeutic agents have shown some success in treating PAH. Such agents include, endothelin receptor antagonists, such as bosentan (TRACLEER®—Acetelion), phosphodiesterase type 5 inhibitors, such as sildenafil citrate (REVATIO®—Pfizer), and prostanoids, such as iloprost (VENTAVIS®—CoTherix/Schering AG), treprostinil sodium (REMODULIN®—United Therapeutics), and epoprostenol sodium (FLOLAN®—Glaxo SmithKline). Some of these drugs are formulated and approved for subcutaneous or intravenous administration and may be delivered subcutaneously or intraveneously via external pump systems. While effective, such external systems can be cumbersome for the patient and can result in injection site pain.
To date, no fully implantable systems are used for delivering therapeutic agents for the treatment of PAH. However, such implantable systems have been used for treatment of a variety of diseases and often improve patient quality of life relative to chronic therapies that do not employ fully implantable systems. Such implantable systems typically include an implantable infusion device and a catheter coupled to the infusion device. One complication experienced with the use of implantable catheters is catheter occlusion resulting from blood ingression and blood clot formation in the catheter lumen. One solution proposed for preventing such occlusion is to incorporate a one-way valve, such as a one-way sleeve valve into a delivery region of a catheter to allow fluid to exit the lumen of the catheter into the body (but not from the body to the lumen). In addition and for purposes of catheter diagnostics, pressure monitors have been proposed that can monitor internal catheter pressure for purposes of diagnosing whether the catheter is obstructed; e.g. kinked or clogged, or contains a leak. However, the use of such pressure sensors for therapeutic purposes has not been described.